PROJECT SUMMARY Stanford Chemistry, Engineering & Medicine for Human Health (ChEM-H) is a new Institute bringing together chemists, engineers, biologists, and clinicians to understand life at the molecular level and to apply that knowledge to improving human health. ChEM-H builds on Stanford's extraordinary talent in the Schools of Humanities & Sciences, Engineering, and Medicine, as well as from the SLAC National Accelerator Laboratory, to explore this new frontier at the interface of chemistry and human biology. In this proposal we request funds from the NIH High End Instrumentation (HEI) S10 Grant Program to purchase a new Bruker Avance Neo 500 MHz NMR Spectrometer with High-Sensitivity CryoProbe and Automated Sample Changer to be sited in the brand-new and centrally located Stanford ChEM-H Building, part of the new ChEM- H / Neuro research complex. The instrument will be accessible and enabling to all researchers at Stanford. Nuclear Magnetic Resonance (NMR) spectroscopy is the single most important routine characterization technique for scientists working in chemistry or at an interface therewith. However, current NMR capabilities on campus are severely limited by the existence of outdated instruments that lack the ability to quickly analyze samples on sub-milligram scales and to do so in a high-throughput manner. Updating current instrumentation is critical to the future research at ChEM-H and across the university. We are requesting the acquisition of a state-of-the-art Bruker NMR system in order to bring much needed modern molecular characterization abilities to campus. A high sensitivity CryoProbe to be included with this acquisition will make possible previously unavailable experiments such as the ability to acquire on low-concentration samples in a reasonable period of time. The requested automated sample changer will dramatically increase the quantity of possible data acquisition by allowing routine experiments to be run unattended around the clock. Overall, the new instrument will be enabling for current and future studies of chemical systems that need to be analyzed and characterized by research groups that include ligands, small molecules, natural products, extracts, inhibitors, drugs, derivatives, tool compounds, libraries, as well as their interrogation within larger molecules (proteins, nucleic acids, polymers, etc.) of interest to ChEM-H and Stanford faculty. The long-term goal of ChEM-H is to explore the biological chemistry frontier in order to better understand human biological systems and to treat disease. In order to achieve this objective, it is critical that NMR capabilities at Stanford are updated through the acquisition of a modern instrument.